Glycine attenuates impairments of stimulus-evoked gamma oscillation in the ketamine model of schizophrenia

A reduction in the early auditory evoked gamma-band response (aeGBR), a type of brain wave, is seen in both schizophrenia patients and healthy people given ketamine, which mimics the brain's excitation/inhibition imbalance thought to underlie the disorder. This change in brain activity is linked to negative symptoms. In a study of 24 healthy men, ketamine alone reduced the aeGBR amplitude and increased negative symptoms as measured by the PANSS scale. Pretreatment with the amino acid glycine lessened both the brain-wave alteration and the symptom increase in those who responded to glycine. The aeGBR may serve as a biomarker to identify schizophrenia patients with negative symptoms who could benefit from glutamatergic treatments.

Study at a glance

Abstract

Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects in the ketamine-model, which addresses the putative excitation / inhibition (E/I) imbalance of the diseases. Moreover, this change in gamma-band oscillations can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment.